Antisense oligonucleotides are modified synthetic oligonucleotides which can inhibit gene expression. For example, antisense oligodeoxynucleotides (ODNs) are modified oligodeoxynucleotides which can inhibit gene expression by interfering with messenger RNA (mRNA) translation. More specifically, many antisense ODNs are designed to bind tightly to mRNA that serves as a template to synthesize a protein. Since the RNA template is known as the "sense" strand, the complementary sequence that binds to it is called the antisense strand. An antisense drug can act, for example, by destroying the targeted mRNA as a result of binding to it, thereby invoking the activity of a ubiquitous cellular enzyme ribonuclease H (RNase H). This enzyme will cleave RNA that is bound to DNA. As such, antisense ODNs are useful, for example, in the treatment of diseases where a particular protein has been identified as critical for a disease to flourish. Many antisense ODNs are modified by replacement of one of the phosphate oxygens in the backbone by a sulfur, so that the antisense ODN is not a poly(phosphodiester) but a poly(phosphorothioate). Antisense ODNs of this type are typically designated [S]ODNs.
Antisense ODNs and other therapeutic oligonucleotides such as, ribozymes, antisense oligoribonucleotides, peptide nucleic acids, decoy RNAs and "dumbbell" DNAs, also known as transcription factor decoy DNAs, are typically administered intravenously. Many conditions which can be treated by oligonucleotide drug therapy require repetitive administration of the oligonucleotide, such as an antisense ODN, which can be problematic with regard to patient compliance.
Therefore, a need exists for a means of delivering oligonucleotides, such as antisense ODNs, which eliminates the need for repetitive administration without inordinately reducing the activity or potency of the ODN released.